117 results on '"Claudio N."'
Search Results
2. Predicting recurrence of major depressive episodes using the Depression Implicit Association Test: A Canadian Biomarker Integration Network in Depression (CAN-BIND) Report
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Rnic, Katerina, primary, LeMoult, Joelle, additional, Torres, Ivan J., additional, Chakrabarty, Trisha, additional, Foster, Jane, additional, Frey, Benicio N., additional, Harkness, Kate L., additional, Ho, Keith, additional, Li, Qingqin S., additional, Milev, Roumen, additional, Quilty, Lena C., additional, Rotzinger, Susan, additional, Soares, Claudio N., additional, Uher, Rudolf, additional, Kennedy, Sidney H., additional, and Lam, Raymond W., additional
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- 2023
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3. Response Inhibition and Predicting Response to Pharmacological and Cognitive Behavioral Therapy Treatments for Major Depressive Disorder: A Canadian Biomarker Integration Network for Depression Study
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Prabhjot Dhami, Lena C. Quilty, Benjamin Schwartzmann, Rudolf Uher, Timothy A. Allen, Stefan Kloiber, Raymond W. Lam, Glenda MacQueen, Benicio N. Frey, Roumen Milev, Daniel J. Müller, Stephen C. Strother, Pierre Blier, Claudio N. Soares, Sagar V. Parikh, Gustavo Turecki, Jane A. Foster, Susan Rotzinger, Sidney H. Kennedy, and Faranak Farzan
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Cognitive Neuroscience ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Biological Psychiatry - Abstract
Major depressive disorder (MDD) is associated with various cognitive impairments, including response inhibition. Deficits in response inhibition may also underlie poor antidepressant treatment response. Recent studies revealed that the neurobiological correlates of response inhibition can predict response to pharmacological treatments. However, the generalizability of this finding to first-line nonpharmacological treatments, particularly cognitive behavioral therapy, remains to be investigated.Data from two independent treatment protocols were combined, one in which 65 patients with MDD underwent treatment with escitalopram, and the other in which 41 patients with MDD underwent a course of cognitive behavioral therapy. A total of 25 healthy control subjects were also recruited. Neural correlates of response inhibition were captured by participants completing a Go/NoGo task during electroencephalography recording. Response inhibition-related measures of interest included the amplitudes of the N2 and P3 event-related potentials.Pretreatment P3 amplitude, which has been linked to both the motor and cognitive aspects of response inhibition, was a significant predictor of change in depressive symptoms following escitalopram and cognitive behavioral therapy treatment. A greater pretreatment P3 amplitude was associated with a greater reduction in depressive severity. In addition, the pretreatment P3 amplitude was found to be significantly greater at baseline in remitters than in nonremitters and healthy control subjects.The integrity of response inhibition may be critical for a successful course of pharmacological or psychological treatment for MDD. Electrophysiological correlates of response inhibition may have utility as a general prognostic marker of treatment response in MDD. Future studies may investigate the benefit of preceding first-line treatments with interventions that improve response inhibition in MDD.
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- 2023
4. Anxiety and depression in midlife transition and beyond: The role of estrogens
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Soares, Claudio N., primary
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- 2023
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5. Stress, Resilience, Moral Distress, and Depression–Anxiety Among Oncology Care Providers in Colombia During the COVID-19 Pandemic
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Martinez, Nicolás, primary, García, María del Pilar, additional, Hanna, Timothy P., additional, Soares, Claudio N., additional, Uribe, Miguel, additional, Sullivan, Richard, additional, Booth, Christopher, additional, and Murillo, Raúl, additional
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- 2023
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6. Acute and chronic stress predict anti-depressant treatment outcome and naturalistic course of major depression: A CAN-BIND report
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Owen Hicks, Shane J. McInerney, Raymond W. Lam, Roumen V. Milev, Benicio N. Frey, Claudio N. Soares, Jane A. Foster, Susan Rotzinger, Sidney H. Kennedy, and Kate L. Harkness
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Adult ,Depressive Disorder, Major ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,Depression ,Recurrence ,Chronic Disease ,Humans ,Antidepressive Agents - Abstract
In treatment studies of major depressive disorder (MDD), exposure to major life events predicts less symptom improvement and greater likelihood of relapse. In contrast, the impact of minor life events has received less attention. We hypothesized that the impact of minor events on symptom improvement and risk of relapse would be heightened in the presence of concurrent chronic stress. We also hypothesized that major events would predict less symptom improvement and greater risk of relapse independently of chronic stress.Adult patients experiencing an episode of MDD were enrolled into a 16-week trial with antidepressant treatments (n = 156). Forty-three fully remitted patients agreed to participate in a naturalistic 18-month follow-up, and 30 had full data for analyses. Life events and chronic stressors were assessed using a contextual life stress interview.Greater exposure to minor events predicted greater improvement in symptoms during acute treatment, but this relation was specific to those who reported greater severity of chronic stress. During follow-up, however, major life events predicted increased risk of relapse, and this effect was not moderated by chronic stress.High attrition rates led to a small sample size for the follow-up analyses.Exposure to minor events may provide an opportunity to practice problem-solving skills, thereby facilitating symptom improvement. Nevertheless, acute treatment did not protect patients from relapse when they subsequently faced major events during follow-up. Therefore, adjunctive strategies may be needed to enhance outcomes during pharmacotherapy, consolidating benefits from acute treatment and providing skills to prevent relapse.
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- 2022
7. 286. Genetic Polymorphism of Brain-Derived Neurotrophic Factor is Related to Antidepressant Efficacy and Treatment-Induced Hippocampal Plasticity in Patients With Major Depressive Disorder: CAN-BIND-1 Study
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Nogovitsyn, Nikita, primary, Fiori, Laura, additional, Rizvi, Sakina J., additional, Ceniti, Amanda K., additional, Ballester, Pedro, additional, Foster, Jane A., additional, Dunlop, Katharine, additional, Ho, Keith, additional, Hassel, Stefanie, additional, Milev, Roumen V., additional, Soares, Claudio N., additional, Strother, Stephen C., additional, Arnott, Stephen R., additional, Lam, Raymond W., additional, Uher, Rudolf, additional, Parikh, Sagar V., additional, Farzan, Faranak, additional, Taylor, Valerie H., additional, MacQueen, Glenda, additional, Mueller, Daniel J., additional, Turecki, Gustavo, additional, Rotzinger, Susan, additional, Frey, Benicio N., additional, and Kennedy, Sidney H., additional
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- 2023
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8. Menopause and Mood
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Soares, Claudio N., primary
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- 2023
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9. Menopause and Mood
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Claudio N. Soares
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Psychiatry and Mental health - Published
- 2023
10. How good are AlphaFold models for docking-based virtual screening?
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Scardino, Valeria, primary, Di Filippo, Juan I., additional, and Cavasotto, Claudio N., additional
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- 2023
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11. EFFECTS OF CYP2C19, CYP2D6, AND ABCB1 GENE VARIANTS ON ESCITALOPRAM AND ARIPIPRAZOLE TREATMENT-RELATED SEXUAL SIDE EFFECTS: RESULTS FROM THE CAN-BIND-1 STUDY
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Islam, Farhana, primary, Magarbeh, Leen, additional, Frey, Benicio N., additional, Milev, Roumen, additional, Soares, Claudio N., additional, Parikh, Sagar, additional, Placenza, Franca, additional, Leri, Francesco, additional, Blier, Pierre, additional, Uher, Rudolf, additional, Farzan, Faranak, additional, Lam, Raymond, additional, Turecki, Gustavo, additional, Kennedy, Sidney, additional, and Mueller, Daniel, additional
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- 2022
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12. Acute and chronic stress predict anti-depressant treatment outcome and naturalistic course of major depression: A CAN-BIND report
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Hicks, Owen, primary, McInerney, Shane J., additional, Lam, Raymond W., additional, Milev, Roumen V., additional, Frey, Benicio N., additional, Soares, Claudio N., additional, Foster, Jane A., additional, Rotzinger, Susan, additional, Kennedy, Sidney H., additional, and Harkness, Kate L., additional
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- 2022
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13. 286. Genetic Polymorphism of Brain-Derived Neurotrophic Factor is Related to Antidepressant Efficacy and Treatment-Induced Hippocampal Plasticity in Patients With Major Depressive Disorder: CAN-BIND-1 Study
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Nikita Nogovitsyn, Laura Fiori, Sakina J. Rizvi, Amanda K. Ceniti, Pedro Ballester, Jane A. Foster, Katharine Dunlop, Keith Ho, Stefanie Hassel, Roumen V. Milev, Claudio N. Soares, Stephen C. Strother, Stephen R. Arnott, Raymond W. Lam, Rudolf Uher, Sagar V. Parikh, Faranak Farzan, Valerie H. Taylor, Glenda MacQueen, Daniel J. Mueller, Gustavo Turecki, Susan Rotzinger, Benicio N. Frey, and Sidney H. Kennedy
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Biological Psychiatry - Published
- 2023
14. EFFECTS OF CYP2C19, CYP2D6, AND ABCB1 GENE VARIANTS ON ESCITALOPRAM AND ARIPIPRAZOLE TREATMENT-RELATED SEXUAL SIDE EFFECTS: RESULTS FROM THE CAN-BIND-1 STUDY
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Farhana Islam, Leen Magarbeh, Benicio N. Frey, Roumen Milev, Claudio N. Soares, Sagar Parikh, Franca Placenza, Francesco Leri, Pierre Blier, Rudolf Uher, Faranak Farzan, Raymond Lam, Gustavo Turecki, Sidney Kennedy, and Daniel Mueller
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Pharmacology ,Psychiatry and Mental health ,Neurology ,Pharmacology (medical) ,Neurology (clinical) ,Biological Psychiatry - Published
- 2022
15. P382. Replication of Personalized Relapse Prediction in Patients With Major Depressive Disorder Using Digital Biomarkers
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Vairavan, Srinivasan, primary, Morrison, Randall L., additional, Drevets, Wayne C., additional, Placenza, Franca, additional, Rotzinger, Susan, additional, Foster, Jane, additional, Soares, Claudio N., additional, Uher, Rudolf, additional, Frey, Benicio N., additional, Milev, Roumen, additional, Lam, Raymond W., additional, Kennedy, Sidney, additional, Narayan, Vaibhav A., additional, and Li, Qingqin, additional
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- 2022
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16. Response Inhibition and Predicting Response to Pharmacological and Cognitive Behavioral Therapy Treatments for Major Depressive Disorder: A Canadian Biomarker Integration Network for Depression Study
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Dhami, Prabhjot, primary, Quilty, Lena C., additional, Schwartzmann, Benjamin, additional, Uher, Rudolf, additional, Allen, Timothy A., additional, Kloiber, Stefan, additional, Lam, Raymond W., additional, MacQueen, Glenda, additional, Frey, Benicio N., additional, Milev, Roumen, additional, Müller, Daniel J., additional, Strother, Stephen C., additional, Blier, Pierre, additional, Soares, Claudio N., additional, Parikh, Sagar V., additional, Turecki, Gustavo, additional, Foster, Jane A., additional, Rotzinger, Susan, additional, Kennedy, Sidney H., additional, and Farzan, Faranak, additional
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- 2022
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17. P382. Replication of Personalized Relapse Prediction in Patients With Major Depressive Disorder Using Digital Biomarkers
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Srinivasan Vairavan, Randall L. Morrison, Wayne C. Drevets, Franca Placenza, Susan Rotzinger, Jane Foster, Claudio N. Soares, Rudolf Uher, Benicio N. Frey, Roumen Milev, Raymond W. Lam, Sidney Kennedy, Vaibhav A. Narayan, and Qingqin Li
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Biological Psychiatry - Published
- 2022
18. Directive clinique n° 422c : Ménopause : Humeur, sommeil et cognition
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Shea, Alison K., primary, Wolfman, Wendy, additional, Fortier, Michel, additional, and Soares, Claudio N., additional
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- 2021
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19. Guideline No. 422c: Menopause: Mood, Sleep, and Cognition
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Shea, Alison K., primary, Wolfman, Wendy, additional, Fortier, Michel, additional, and Soares, Claudio N., additional
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- 2021
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20. Hypothalamus volume and DNA methylation of stress axis genes in major depressive disorder: A CAN-BIND study report
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Suh, Jee Su, primary, Fiori, Laura M., additional, Ali, Mohammad, additional, Harkness, Kate L., additional, Ramonas, Milita, additional, Minuzzi, Luciano, additional, Hassel, Stefanie, additional, Strother, Stephen C., additional, Zamyadi, Mojdeh, additional, Arnott, Stephen R., additional, Farzan, Faranak, additional, Foster, Jane A., additional, Lam, Raymond W., additional, MacQueen, Glenda M., additional, Milev, Roumen, additional, Müller, Daniel J., additional, Parikh, Sagar V., additional, Rotzinger, Susan, additional, Sassi, Roberto B., additional, Soares, Claudio N., additional, Uher, Rudolf, additional, Kennedy, Sidney H., additional, Turecki, Gustavo, additional, and Frey, Benicio N., additional
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- 2021
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21. The Midlife Transition, Depression, and Its Clinical Management
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Soares, Claudio N., primary and Shea, Alison K., additional
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- 2021
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22. Premenstrual Dysphoric Disorder: Contemporary Diagnosis and Management
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Claudio N. Soares and Robert L. Reid
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medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,Salpingo-oophorectomy ,Obstetrics and Gynecology ,Cognition ,Affect (psychology) ,medicine.disease ,Clinical trial ,Menstruation ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Etiology ,Humans ,Medicine ,Female ,Clinical significance ,Premenstrual Dysphoric Disorder ,business ,Psychiatry ,Premenstrual dysphoric disorder ,Selective Serotonin Reuptake Inhibitors ,030217 neurology & neurosurgery ,Diet Therapy - Abstract
Most ovulatory women experience premenstrual symptoms (premenstrual syndrome, molimina) which indicate impending menstruation and are of little clinical relevance because they do not affect quality of life. A few women, however, experience significant physical and/or psychological symptoms before menstruation that, if left untreated, would result in deterioration in functioning and relationships. The precise etiology remains elusive, although new theories are gaining support in pre-clinical and early clinical trials. Refined diagnostic criteria allow better discrimination of this condition from other psychiatric diagnoses and the selection of symptom appropriate therapies that afford relief for most women. Pharmacotherapies (particularly selective serotonin reuptake inhibitors and SNRIs) represent the first-line treatment for premenstrual dysphoric disorder and severe, mood-related premenstrual syndrome. Continuous combined oral contraceptives have limited evidence for usefulness in premenstrual dysphoric disorder, whereas medical ovarian suppression is often recommended for patients who fail to respond or cannot tolerate first-line treatments (e.g., selective serotonin reuptake inhibitors). The use of cognitive behavioural therapies is promising, but it remains limited by sparse data and restricted access to trained professionals. A proper diagnosis (particularly the distinction from other underlying psychiatric conditions) is crucial for the implementation of effective therapy and alleviation of this impairing condition.
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- 2018
23. Structure-based drug design for envelope protein E2 uncovers a new class of bovine viral diarrhea inhibitors that block virus entry
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Emilse Soledad Leal, Fernando Merwaiss, Claudio N. Cavasotto, María José Pascual, Mariela Bollini, Maria Eugenia Quintana, Alejandra Victoria Capozzo, and Diego E. Alvarez
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Models, Molecular ,0301 basic medicine ,viruses ,030106 microbiology ,Molecular Conformation ,Biology ,Antiviral Agents ,PESTIVIRUS ,Virus ,REPORTER VIRUS ,Cell Line ,purl.org/becyt/ford/1 [https] ,Ciencias Biológicas ,Structure-Activity Relationship ,03 medical and health sciences ,Viral Envelope Proteins ,Viral envelope ,Viral entry ,Virology ,Animals ,DOCKING ,VIRTUAL SCREENING ,Binding site ,purl.org/becyt/ford/1.6 [https] ,BVDV ,Polymerase ,Pharmacology ,Virtual screening ,Binding Sites ,Diarrhea Viruses, Bovine Viral ,ANTIVIRALS ,Pestivirus ,Virus Internalization ,biology.organism_classification ,030104 developmental biology ,Docking (molecular) ,Drug Design ,biology.protein ,Cattle ,Virología ,CIENCIAS NATURALES Y EXACTAS ,Protein Binding - Abstract
Antiviral targeting of virus envelope proteins is an effective strategy for therapeutic intervention of viral infections. Here, we took a computer-guided approach with the aim of identifying new antivirals against the envelope protein E2 of bovine viral diarrhea virus (BVDV). BVDV is an enveloped virus with an RNA genome responsible for major economic losses of the cattle industry worldwide. Based on the crystal structure of the envelope protein E2, we defined a binding site at the interface of the two most distal domains from the virus membrane and pursued a hierarchical docking-based virtual screening search to identify small-molecule ligands of E2. Phenyl thiophene carboxamide derivative 12 (PTC12) emerged as a specific inhibitor of BVDV replication from in vitro antiviral activity screening of candidate molecules, displaying an IC 50 of 0.30 μM against the reference NADL strain of the virus. Using reverse genetics we constructed a recombinant BVDV expressing GFP that served as a sensitive reporter for the study of the mechanism of action of antiviral compounds. Time of drug addition assays showed that PTC12 inhibited an early step of infection. The mechanism of action was further dissected to find that the compound specifically acted at the internalization step of virus entry. Interestingly, we demonstrated that similar to PTC12, the benzimidazole derivative 03 (BI03) selected in the virtual screen also inhibited internalization of BVDV. Furthermore, docking analysis of PTC12 and BI03 into the binding site revealed common interactions with amino acid residues in E2 suggesting that both compounds could share the same molecular target. In conclusion, starting from a targeted design strategy of antivirals against E2 we identified PTC12 as a potent inhibitor of BVDV entry. The compound can be valuable in the design of antiviral strategies in combination with already well-characterized polymerase inhibitors of BVDV. Fil: Pascual, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Merwaiss, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Leal, Emilse Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Quintana, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina Fil: Capozzo, Alejandra Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina Fil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
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- 2018
24. Artificial intelligence in the early stages of drug discovery
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Cavasotto, Claudio N., primary and Di Filippo, Juan I., additional
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- 2021
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25. Functional and druggability analysis of the SARS-CoV-2 proteome
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Cavasotto, Claudio N., primary, Lamas, Maximiliano Sánchez, additional, and Maggini, Julián, additional
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- 2021
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26. Chromosomal segments may explain the antibody response cooperation for canine leishmaniasis pathogenesis
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Batista, Luís F.S., primary, Torrecilha, Rafaela B.P., additional, Silva, Rafaela B., additional, Utsunomiya, Yuri T., additional, Silva, Thaís B.F., additional, Tomokane, Thaíse Y., additional, Pacheco, Acácio D., additional, Bosco, Anelise M., additional, Paulan, Silvana C., additional, Rossi, Claudio N., additional, Costa, Gustavo N.O., additional, Marcondes, Mary, additional, Ciarlini, Paulo C., additional, Nunes, Cáris M., additional, Matta, Vânia L.R., additional, and Laurenti, Márcia D., additional
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- 2020
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27. Guideline No. 422c: Menopause: Mood, Sleep, and Cognition
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Claudio N. Soares, Alison K. Shea, Wendy Wolfman, and Michel Fortier
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education.field_of_study ,medicine.medical_specialty ,Sleep hygiene ,business.industry ,medicine.medical_treatment ,Black cohosh ,Population ,Obstetrics and Gynecology ,medicine.disease ,Pittsburgh Sleep Quality Index ,Menopause ,medicine ,Major depressive disorder ,Hormone therapy ,Cognitive decline ,education ,Psychiatry ,business - Abstract
Objective Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. Target Population Perimenopausal and postmenopausal women. Benefits, Harms, and Costs Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. Evidence Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002–2020, and MeSH search terms were specific for each topic developed through the 7 chapters. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population. SUMMARY STATEMENTS 1 The perimenopausal period is a window of vulnerability for the development of depressive symptoms and major depressive episodes, even in women with no history of depression (high). 2 Factors related and unrelated to menopause contribute to the occurrence and severity of mood symptoms in mid-life. Factors related to menopause are those that are context-related or timing-related, such as vasomotor symptoms, sleep disturbances, and health problems, whereas those unrelated to menopause represent a continuum of risk that precedes menopause, or longitudinal risk factors, such as unemployment, smoking, and lifetime history of anxiety (high). 3 Recent large-scale studies show an elevated risk of depression in women following hysterectomy, with or without oophorectomy. A history of primary ovarian insufficiency, which occurs in 1% of women, is also associated with an increased risk of depression (high). 4 Poor sleep quality, as measured both subjectively and objectively, is common among women in the perimenopausal and postmenopausal periods (high). 5 Cognitive symptoms, such as worsening memory and slower cognitive speed, are often reported among newly menopausal women, and these symptoms have been demonstrated in prospective, longitudinal studies (moderate). RECOMMENDATIONS 1 Proven therapeutic options for depression at any life stage (i.e., antidepressants, cognitive behavioural therapy, and other behaviour-based psychotherapies) should remain the first-line treatment options for depressive symptoms and episodes during the menopausal transition and postmenopausal years (strong, high). 2 For women experiencing recurrent episodes of depression during the perimenopausal period, selection of antidepressants should consider the patient's response to and toleration of previous trials of antidepressants (strong, moderate). 3 For women experiencing new-onset depression, both adverse effects (e.g., sexual dysfunction, weight changes) and drug–drug interactions (e.g., between specific selective serotonin reuptake inhibitors and tamoxifen) specific to this population should be considered (strong, moderate). 4 There is some evidence that hormone therapy has antidepressant effects similar in magnitude to those observed with classic antidepressant agents in perimenopausal women with depression, with or without concomitant vasomotor symptoms (strong, high). However, hormone therapy is ineffective in treating depressive disorders in postmenopausal women, suggesting a possible window of opportunity for the antidepressant benefits of hormone therapy in perimenopause (strong, moderate). 5 The approach to poor sleep during the menopausal transition should initially include education about sleep hygiene, and primary sleep disorders should be ruled out (strong, high). 6 Vasomotor symptoms are a significant contributor to sleep disruption and should be addressed; hormone therapy may improve sleep when vasomotor symptoms are present (strong, high). 7 Several other therapies for sleep have shown benefit, including cognitive behavioural therapy–insomnia (strong, high), aerobic exercise, eszopiclone, venlafaxine, black cohosh, and valerian root (strong, moderate). 8 For women with cognitive complaints, lifestyle modifications are recommended to decrease the risk of cognitive decline. These include increasing aerobic exercise and including vegetables in the diet more often, as well as limiting the potential influence of hypertension, diabetes, and atherosclerotic disease (strong, high). 9 Menopausal hormone therapy has not been shown to significantly improve measures of cognitive function over several years of use (strong, moderate).
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- 2021
28. Directive clinique n° 422c : Ménopause : Humeur, sommeil et cognition
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Claudio N. Soares, Alison K. Shea, Wendy Wolfman, and Michel Fortier
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Gynecology ,medicine.medical_specialty ,business.industry ,Obstetrics and Gynecology ,Medicine ,business - Abstract
RESUME Objectif Proposer des strategies fondees sur les plus recentes donnees publiees pour ameliorer les soins aux femmes menopausees ou en perimenopause. Population cible Les femmes menopausees ou en perimenopause. Benefices, risques et couts La population cible beneficiera des plus recentes donnees scientifiques publiees communiquees par leurs fournisseurs de soins de sante. Aucun cout ni prejudice ne sont associes a cette information, car les femmes seront libres de choisir parmi les differentes options therapeutiques, y compris le statu quo, pour la prise en charge des symptomes et morbidites associes a la menopause. Donnees probantes Les auteurs ont interroge les bases de donnees PubMed, MEDLINE et Cochrane Library pour extraire des articles publies entre 2002 et 2020 en utilisant des termes MeSH specifiques a chacun des sujets abordes dans les 7 chapitres. Methodes de validation Les auteurs ont evalue la qualite des donnees probantes et la force des recommandations en utilisant l'approche d’evaluation, de developpement et d’evaluation (GRADE). Voir l'annexe A en ligne ( tableau A1 pour les definitions et tableau A2 pour l'interpretation des recommandations fortes et conditionnelles [faibles]). Professionnels concernes gynecologues, obstetriciens, medecins de famille, internistes, urgentologues, infirmieres (autorisees et praticiennes), pharmaciens, stagiaires (etudiants en medecine, residents, moniteurs cliniques) et autres fournisseurs de soins de sante pour la population cible. DECLARATIONS SOMMAIRES 1 La perimenopause est une periode particulierement propice a la manifestation de symptomes depressifs et d’episodes depressifs caracterises, meme chez les femmes sans antecedent de depression (elevee). 2 Des facteurs lies ou non a la menopause contribuent a la manifestation et a l'intensite des symptomes thymiques autour de la cinquantaine. Les facteurs lies a la menopause se rapportent au contexte ou au moment, notamment les symptomes vasomoteurs, les troubles du sommeil et les problemes de sante, tandis que les facteurs qui ne sont pas lies a la menopause s'inscrivent dans un continuum de risques anterieurs a la menopause ou sont des facteurs de risque longitudinaux, comme le chomage, le tabagisme et les antecedents d'anxiete de longue date (elevee). 3 De recentes etudes de grande envergure revelent un risque eleve de depression chez les femmes apres avoir subi une hysterectomie, avec ou sans ovariectomie. Les antecedents d'insuffisance ovarienne primitive, qui survient chez 1 % des femmes, sont egalement associes a une augmentation du risque de depression (elevee). 4 Le sommeil de mauvaise qualite, d'apres une evaluation subjective et objective, est frequent chez les femmes en perimenopause ou menopausees (elevee). 5 Il n'est pas rare que des symptomes cognitifs, comme la deterioration de la memoire et le ralentissement de la cognition, se manifestent chez les femmes au debut de la postmenopause, et ces symptomes ont ete observes dans des etudes prospectives longitudinales (moyenne). RECOMMANDATIONS 1 Il est conseille que les options therapeutiques eprouvees pour la depression a tout moment de la vie (p. ex., antidepresseurs, therapie cognitivo-comportementale et autres psychotherapies comportementales) demeurent les options de traitement de premiere intention pour les symptomes et episodes depressifs pendant la transition menopausique et la postmenopause (forte, elevee). 2 Pour les femmes qui vivent des episodes recurrents de depression pendant la perimenopause, il y a lieu de prendre en compte leur reponse et tolerabilite aux antidepresseurs precedemment utilises au moment de selectionner un antidepresseur (forte, moyenne). 3 Chez les femmes atteintes d'un premier episode de depression, on doit tenir compte des effets indesirables des antidepresseurs (p. ex., dysfonction sexuelle, variation du poids) et des interactions medicamenteuses (p. ex., entre certains ISRS et le tamoxifene) specifiques a cette population (fortes, moderees). 4 Certaines donnees indiquent que l'hormonotherapie a des effets antidepresseurs d'une ampleur semblable a celle des agents antidepresseurs classiques lorsqu'ils sont administres aux femmes en perimenopause atteintes de depression avec ou sans symptomes vasomoteurs concomitants (forte, elevee). Cependant, l'hormonotherapie est inefficace pour traiter les troubles depressifs chez les femmes menopausees, ce qui suggere une periode propice aux effets antidepresseurs de l'hormonotherapie en perimenopause (forte, moderee). 5 Pour les femmes ayant un sommeil de mauvaise qualite pendant la transition menopausique, il y a lieu d'adopter une strategie visant d'abord l’education en matiere d'hygiene du sommeil et l'exclusion des troubles du sommeil primaires (forte, elevee). 6 Les symptomes vasomoteurs constituent un important facteur de perturbation du sommeil et doivent donc etre traites; l'hormonotherapie peut ameliorer le sommeil en cas de symptomes vasomoteurs (forte, elevee). 7 Plusieurs autres traitements se sont averes benefiques pour ameliorer la qualite du sommeil, notamment la therapie cognitivo-comportementale de l'insomnie (forte, elevee), l'exercice aerobique, l'eszopiclone, la venlafaxine, l'actee a grappes noires et la racine de valeriane (forte, moyenne). 8 Pour les femmes qui expriment une plainte cognitive, le changement des habitudes de vie est recommande afin de reduire le risque de declin cognitif. Il est notamment conseille de pratiquer des exercices aerobiques et de manger des legumes plus souvent, en plus de limiter les consequences potentielles de l'hypertension, du diabete et de la maladie atherosclereuse (forte, elevee). 9 Les donnees probantes indiquent que l'hormonotherapie menopausique sur plusieurs annees d'utilisation n'ameliore pas significativement les mesures de la fonction cognitive (forte, moyenne).
- Published
- 2021
29. Hipertensión arterial en el paciente quirúrgico. Adecuación de la medicación y criterios de suspensión
- Author
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Matoses-Jaén, M.S., primary, García-Claudio, N., additional, Álvarez-Escudero, J., additional, and Argente-Navarro, P., additional
- Published
- 2020
- Full Text
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30. Reverse translation of major depressive disorder symptoms: A framework for the behavioural phenotyping of putative biomarkers
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Daniels, Stephen, primary, Horman, Thomas, additional, Lapointe, Thomas, additional, Melanson, Brett, additional, Storace, Alexandra, additional, Kennedy, Sidney H., additional, Frey, Benicio N, additional, Rizvi, Sakina J, additional, Hassel, Stefanie, additional, Mueller, Daniel J, additional, Parikh, Sagar V, additional, Lam, Raymond W, additional, Blier, Pierre, additional, Farzan, Faranak, additional, Giacobbe, Peter, additional, Milev, Roumen, additional, Placenza, Franca, additional, Soares, Claudio N, additional, Turecki, Gustavo, additional, Uher, Rudolf, additional, and Leri, Francesco, additional
- Published
- 2020
- Full Text
- View/download PDF
31. A discussion of potential clinical markers predicting anti-inflammatory treatment response in individuals with major depression
- Author
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Brietzke, Elisa, primary, Booij, Linda, additional, Wieck, Andrea, additional, Ricci, Alessandro, additional, Soares, Claudio N., additional, Roberts, Nasreen, additional, and Khalid-Khan, Sarosh, additional
- Published
- 2020
- Full Text
- View/download PDF
32. Depression and Menopause
- Author
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Claudio N. Soares
- Subjects
medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,Vulnerability ,Luteal phase ,medicine.disease ,Menopause ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Economic cost ,Menopause transition ,Medicine ,Anxiety ,medicine.symptom ,business ,Psychiatry ,030217 neurology & neurosurgery ,Depression (differential diagnoses) ,Postpartum period - Abstract
Depression is a disabling condition, which often leads to significant personal, societal, and economic costs. Windows of vulnerability for depression in women likely are associated with an increased sensitivity experienced by some women to changes in the hormonal milieu that occur during the luteal phase of their cycles, during the postpartum period, and/or during the menopause transition. The controversy surrounding a menopause-related depression has been fueled by conflicting methodologies used to characterize reproductive staging or assess psychiatric conditions during midlife years.
- Published
- 2017
33. Subtle persistent working memory and selective attention deficits in women with premenstrual syndrome
- Author
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Benicio N. Frey, Geoffrey B. Hall, Claudio N. Soares, Meir Steiner, Anastasiya Slyepchenko, Brianne Nicholls, and Sonali Lokuge
- Subjects
Adult ,Sleep Wake Disorders ,Pediatrics ,medicine.medical_specialty ,Adolescent ,media_common.quotation_subject ,Luteal Phase ,Neuropsychological Tests ,Luteal phase ,Asymptomatic ,050105 experimental psychology ,Premenstrual Syndrome ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Follicular phase ,medicine ,Humans ,Attention ,0501 psychology and cognitive sciences ,Young adult ,Psychiatry ,Menstrual Cycle ,Biological Psychiatry ,Menstrual cycle ,media_common ,Memory Disorders ,Working memory ,05 social sciences ,Psychiatry and Mental health ,Memory, Short-Term ,Mood ,Follicular Phase ,Female ,medicine.symptom ,Psychology ,Neurocognitive ,030217 neurology & neurosurgery - Abstract
As a recurrent, cyclical phenomenon, premenstrual syndrome (PMS) affects a significant proportion of women of the reproductive age, and leads to regular monthly days of functional impairment. Symptoms of PMS include somatic and psychological symptoms, such as headaches, sleep disturbances, social withdrawal and mood changes, during the late luteal phase of the menstrual cycle, which alleviate during the follicular phase. This study investigated neurocognitive functioning in women with moderate to severe PMS symptoms (n=13) compared to women with mild/no PMS (n=27) through administration of a battery of neuropsychological tests during the asymptomatic follicular phase of the menstrual cycle. Relative to women with mild/no PMS symptoms, women with moderate to severe PMS showed significantly poorer accuracy and more errors of omission on the N-0-back, as well as more errors of omission on the N-2-back task, indicating the presence of impairment in selective attention and working memory. This study provides evidence of persistent, subtle working memory and selective attention difficulties in those with moderate to severe PMS during the follicular phase of the menstrual cycle.
- Published
- 2017
34. A discussion of potential clinical markers predicting anti-inflammatory treatment response in individuals with major depression
- Author
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Claudio N. Soares, Linda Booij, Alessandro Ricci, Andrea Wieck, Nasreen Roberts, Sarosh Khalid-Khan, and Elisa Brietzke
- Subjects
Oncology ,Depressive Disorder, Major ,medicine.medical_specialty ,Depression ,Endocrine and Autonomic Systems ,business.industry ,Anti inflammatory treatment ,Immunology ,Anti-Inflammatory Agents ,MEDLINE ,Behavioral Neuroscience ,Text mining ,Internal medicine ,medicine ,Humans ,business ,Biomarkers ,Depression (differential diagnoses) - Published
- 2020
35. Functional and druggability analysis of the SARS-CoV-2 proteome
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Claudio N. Cavasotto, Maximiliano Sánchez Lamas, and Julián Maggini
- Subjects
Models, Molecular ,0301 basic medicine ,Proteases ,Proteome ,viruses ,In silico ,Druggability ,SARS-COV-2 ,Disease ,Computational biology ,Biology ,medicine.disease_cause ,Antiviral Agents ,Ciencias Biológicas ,purl.org/becyt/ford/1 [https] ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Full Length Article ,Pandemic ,medicine ,Humans ,purl.org/becyt/ford/1.6 [https] ,DRUGGABILITY ,Polymerase ,Binding hot-spots ,Coronavirus ,Pharmacology ,Binding Sites ,SARS-CoV-2 ,Drug discovery ,fungi ,COVID-19 ,COVID-19 Drug Treatment ,PROTEOME ,030104 developmental biology ,biology.protein ,Virología ,CIENCIAS NATURALES Y EXACTAS ,030217 neurology & neurosurgery - Abstract
The infectious coronavirus disease (COVID-19) pandemic, caused by the coronavirus SARS-CoV-2, appeared in December 2019 in Wuhan, China, and has spread worldwide. As of today, more than 46 million people have been infected and over 1.2 million fatalities. With the purpose of contributing to the development of effective therapeutics, we performed an in silico determination of binding hot-spots and an assessment of their druggability within the complete SARS-CoV-2 proteome. All structural, non-structural, and accessory proteins have been studied, and whenever experimental structural data of SARS-CoV-2 proteins were not available, homology models were built based on solved SARS-CoV structures. Several potential allosteric or protein-protein interaction druggable sites on different viral targets were identified, knowledge that could be used to expand current drug discovery endeavors beyond the currently explored cysteine proteases and the polymerase complex. It is our hope that this study will support the efforts of the scientific community both in understanding the molecular determinants of this disease and in widening the repertoire of viral targets in the quest for repurposed or novel drugs against COVID-19., Graphical abstract Image 1
- Published
- 2021
36. Pre-Treatment Resting-State Functional Connectivity Related to Anhedonia and Anxiety are Associated With Antidepressant Response to Escitalopram and Adjunct Aripiprazole
- Author
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Roumen Milev, Rudolf Uher, Claudio N. Soares, Sagar V. Parikh, Katharine Dunlop, Gustavo Turecki, Susan Rotzinger, Sidney H. Kennedy, Stephen C. Strother, Raymond W. Lam, Sakina J. Rizvi, Glenda MacQueen, Benicio N. Frey, Conor Liston, and Stefanie Hassel
- Subjects
medicine.medical_specialty ,Resting state fMRI ,business.industry ,Functional connectivity ,Anhedonia ,Adjunct ,medicine ,Escitalopram ,Anxiety ,Antidepressant ,Aripiprazole ,medicine.symptom ,Psychiatry ,business ,Biological Psychiatry ,medicine.drug - Published
- 2020
37. Integrated Genome-Wide Methylation and Expression Analyses Reveal Functional Predictors of Response to Antidepressants
- Author
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Claudio N. Soares, Roumen Milev, Faranak Farzan, Daniel J. Müller, Sidney H. Kennedy, Rudolf Uher, Jean-François Théroux, Francesco Leri, Laura M. Fiori, Raymond W. Lam, Qingqin Li, Chelsey Ju, Susan Rotzinger, Raoul Belzeaux, Sagar V. Parikh, Pierre Blier, Peter Giacobbe, Glenda MacQueen, Jane A. Foster, Gustavo Turecki, Benicio N. Frey, Zahia Aouabed, and Gary Gang Chen
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.disease ,Clinical trial ,Internal medicine ,DNA methylation ,Cohort ,medicine ,Major depressive disorder ,Biomarker (medicine) ,Escitalopram ,Epigenetics ,business ,Depression (differential diagnoses) ,medicine.drug - Abstract
Background: Major depressive disorder (MDD) is primarily treated with antidepressants, yet many patients fail to respond to adequate trials. Understanding who is likely to respond to antidepressant treatment and/or what mediates this response is of considerable clinical importance. As part of the Canadian Biomarker Integration Network in Depression (CAN-BIND-1) initiative, we aimed to identify differential DNA methylation marks as epigenetic predictors of antidepressant response (ADR) in MDD patients. Methods: Healthy participants (n=112) and depressed participants (n=211) between 18-60 years of age were recruited across six Canadian clinical centers. Eligible depressed patients with MDD by DSM-IV-TR criteria and a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥24 were enrolled. Genome-wide DNA methylation analysis was conducted using the Infinium MethylationEPIC Beadchipb with DNA extracted from baseline peripheral blood samples prior to beginning an eight-week trial of escitalopram. Genome-wide mRNA expression analysis was conducted on the HumanHT-12 v4 Expression Beadchip in RNA extracted from leukocytes at baseline. Depressed patients were classified as non-responders (NRES) and responders (RES) according to changes in MADRS scores following eight weeks of treatment. Differentially methylated positions (DMPs) were identified in regions of differentially expressed genes and validated using a targeted sequencing approach. Replication was conducted with patients participating in a similar trial, the Douglas Biomarker Study. CAN-BIND-1 clinical trial was registered with the ClinicalTrials.gov identification #: NCT101655706. Findings: After depressed participants concluded the 8-week trial, 82 RES and 95 NRES were included in this study. Genome-wide differential DNA methylation revealed 2,572 DMPs (p
- Published
- 2018
38. S124. Impact of CYP2C19 and CYP2D6 Genotypes on Clinical Outcomes and Side Effects in Patients Receiving Escitalopram and Aripiprazole for Major Depression: Results From the Can-Bind Cohort
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Sidney H. Kennedy, Gustavo Turecki, Roumen Milev, Claudio N. Soares, Malgorzata Maciukiewicz, Daniel J. Mueller, Victoria S. Marshe, Sagar V. Parikh, Susan Rotzinger, Glenda MacQueen, Benicio N. Frey, Farhana Islam, Jane A. Foster, Raymond W. Lam, Rudolf Uher, and Kazunari Yoshida
- Subjects
medicine.medical_specialty ,CYP2D6 ,business.industry ,CYP2C19 ,Internal medicine ,Genotype ,Cohort ,Medicine ,Escitalopram ,In patient ,Aripiprazole ,business ,Biological Psychiatry ,Depression (differential diagnoses) ,medicine.drug - Published
- 2019
39. De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus
- Author
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Leal, Emilse S., primary, Adler, Natalia S., additional, Fernández, Gabriela A., additional, Gebhard, Leopoldo G., additional, Battini, Leandro, additional, Aucar, Maria G., additional, Videla, Mariela, additional, Monge, María Eugenia, additional, Hernández de los Ríos, Alejandro, additional, Acosta Dávila, John Alejandro, additional, Morell, María L., additional, Cordo, Sandra M., additional, García, Cybele C., additional, Gamarnik, Andrea V., additional, Cavasotto, Claudio N., additional, and Bollini, Mariela, additional
- Published
- 2019
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40. Depression and Menopause
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Soares, Claudio N., primary
- Published
- 2019
- Full Text
- View/download PDF
41. Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description
- Author
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Francesca Spyrakis and Claudio N. Cavasotto
- Subjects
Virtual screening ,Protein Conformation ,Computer science ,Active site water molecules ,Homology modeling ,Ligand docking ,Protein flexibility ,Structure-based drug discovery ,Catalytic Domain ,Computer Simulation ,Receptors, Cell Surface ,Water ,Molecular Docking Simulation ,Biochemistry ,Biophysics ,Molecular Biology ,Nanotechnology ,Receptors ,HOMOLOGY MODELING ,Conceptual frame ,VIRTUAL SCREENING ,DOCKING ,Medicine (all) ,Otras Ciencias Químicas ,Ciencias Químicas ,STRUCTURE-BASED DRUG DESIGN ,Cell Surface ,Systems engineering ,Structure based ,CIENCIAS NATURALES Y EXACTAS - Abstract
Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical “structural” issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Fil: Spyrakis, Francesca. Università degli Studi di Modena e Reggio Emilia; Italia Fil: Cavasotto, Claudio Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
- Published
- 2015
42. RETIRED: Managing Menopause Abstract and Summary Statement
- Author
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Robert Reid, Beth L. Abramson, Jennifer Blake, Sophie Desindes, Sylvie Dodin, Shawna Johnston, Timothy Rowe, Namrita Sodhi, Penny Wilks, Wendy Wolfman, Claudio N. Soares, Michel Fortier, Lisa Graves, Bing Guthrie, and Aliya Khan
- Subjects
medicine.medical_specialty ,business.industry ,Obstetrics and Gynecology ,Guideline ,Cochrane Library ,law.invention ,Clinical trial ,Systematic review ,Randomized controlled trial ,law ,Family medicine ,Health care ,Medicine ,Observational study ,Medical prescription ,business - Abstract
Objective To provide updated guidelines for health care providers on the management of menopause in asymptomatic healthy women as well as in women presenting with vasomotor or urogenital symptoms and on considerations related to cardiovascular disease, breast cancer, urogynaecology, and sexuality. Outcomes Lifestyle interventions, prescription medications, and complementary and alternative therapies are presented according to their efficacy in the treatment of menopausal symptoms. Counselling and therapeutic strategies for sexuality concerns in the peri- and postmenopausal years are reviewed. Approaches to the identification and evaluation of women at high risk of osteoporosis, along with options for prevention and treatment, are presented in the companion osteoporosis guideline. Evidence Published literature was retrieved through searches of PubMed and The Cochrane Library in August and September 2012 with the use of appropriate controlled vocabulary (e.g., hormone therapy, menopause, cardiovascular diseases, and sexual function) and key words (e.g., hormone therapy, perimenopause, heart disease, and sexuality). Results were restricted to clinical practice guidelines, systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Results were limited to publication dates of 2009 onwards and to material in English or French. Searches were updated on a regular basis and incorporated in the guideline until January 5, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, national and international medical specialty societies, and clinical practice guideline collections. Values The quality of the evidence in this document was rated using the criteria described by the Report of the Canadian Task Force on Preventive Health Care (Table 1).
- Published
- 2014
43. De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus
- Author
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Cybele C. García, Claudio N. Cavasotto, Leandro Battini, John Acosta Dávila, Natalia S. Adler, María L. Morell, M. Videla, Leopoldo German Gebhard, Emilse Soledad Leal, Alejandro Hernández de los Ríos, Sandra M. Cordo, María Gabriela Aucar, María Eugenia Monge, Andrea V. Gamarnik, Gabriela Araceli Fernandez, and Mariela Bollini
- Subjects
Models, Molecular ,Cell Survival ,In silico ,Cell ,ANTI-DENGUE VIRUS COMPOUNDS ,Microbial Sensitivity Tests ,Dengue virus ,medicine.disease_cause ,Antiviral Agents ,01 natural sciences ,Cell Line ,Dengue fever ,purl.org/becyt/ford/1 [https] ,Small Molecule Libraries ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,Viral Envelope Proteins ,PHARMACOKINETICS IN VITRO PROPERTIES ,Viral entry ,Drug Discovery ,purl.org/becyt/ford/1.4 [https] ,medicine ,Animals ,Humans ,DE NOVO DESIGN ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,General Medicine ,Dengue Virus ,medicine.disease ,Small molecule ,Virology ,In vitro ,0104 chemical sciences ,medicine.anatomical_structure ,Solubility ,A549 Cells ,Drug Design ,MOLECULAR DYNAMICS ,Viral disease - Abstract
Dengue fever is a mosquito-borne viral disease that has become a major public health concern worldwide. This disease presents with a wide range of clinical manifestations, from a mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, neither an approved drug nor an effective vaccine for the treatment are available to fight the disease. The envelope protein (E) is a major component of the virion surface. This protein plays a key role during the viral entry process, constituting an attractive target for the development of antiviral drugs. The crystal structure of the E protein reveals the existence of a hydrophobic pocket occupied by the detergent n-octyl-β-d-glucoside (β-OG). This pocket lies at the hinge region between domains I and II and is important for the low pH-triggered conformational rearrangement required for the fusion of the virion with the host's cell. Aiming at the design of novel molecules which bind to E and act as virus entry inhibitors, we undertook a de novo design approach by “growing” molecules inside the hydrophobic site (β-OG). From more than 240000 small-molecules generated, the 2,4 pyrimidine scaffold was selected as the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like physicochemical and in vitro pharmacokinetic properties revealed that compounds 3e and 3h presented acceptable solubility values and were stable in mouse plasma, simulated gastric fluid, simulated intestinal fluid, and phosphate buffered saline solution. Fil: Leal, Emilse Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Adler, Natalia Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina Fil: Fernandez, Gabriela Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Gebhard, Leopoldo German. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Battini, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Aucar, María Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina Fil: Videla, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Hernández de los Ríos, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Acosta Dávila, John. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Morell, María L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: García, Cybele C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Gamarnik, Andrea Vanesa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cavasotto, Claudio Norberto. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad Austral; Argentina Fil: Bollini, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina
- Published
- 2019
44. M31 IMPACT OF CYP2C19 AND CYP2D6 GENE VARIANTS ON PLASMA LEVELS AND TREATMENT RESPONSE IN PATIENTS RECEIVING ESCITALOPRAM AND ARIPIPRAZOLE FOR MAJOR DEPRESSION: RESULTS FROM THE CAN-BIND-1 COHORT
- Author
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Claudio N. Soares, Victoria S. Marshe, Malgorzata Maciukiewicz, Daniel J. Mueller, Raymond W. Lam, Susan Rotzinger, Roumen Milev, Sidney H. Kennedy, Sagar V. Parikh, Farhana Islam, Rudolf Uher, Gustavo Turecki, Glenda MacQueen, Benicio N. Frey, and Jane A. Foster
- Subjects
Pharmacology ,Oncology ,medicine.medical_specialty ,Treatment response ,business.industry ,CYP2D6 Gene ,Plasma levels ,CYP2C19 ,Psychiatry and Mental health ,Neurology ,Internal medicine ,Cohort ,medicine ,Escitalopram ,Pharmacology (medical) ,Aripiprazole ,Neurology (clinical) ,business ,Biological Psychiatry ,Depression (differential diagnoses) ,medicine.drug - Published
- 2019
45. F107. Cortical Thickness Features Differentiate 16-Week Antidepressant Response Profiles in Major Depressive Disorder
- Author
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Roberto B. Sassi, Zahinoor Ismail, Claudio N. Soares, Faranak Farzan, Daniel J. Mueller, Roumen Milev, Jacqueline K. Harris, Gulshan B. Sharma, Glenda MacQueen, Stephen R. Arnott, Benicio N. Frey, Jane A. Foster, Luciano Minuzzi, Stefanie Hassel, Susan Rotzinger, Geoffrey B. Hall, Sidney H. Kennedy, Jee Su Suh, Raymond W. Lam, Kate L. Harkness, Jonathan Downar, Gésine L. Alders, Pierre Blier, Andrew D. Davis, Pradeep Reddy Raamana, Peter Giacobbe, Shane McInerney, Sagar V. Parikh, Rudolf Uher, Mojdeh Zamyadi, Gustavo Turecki, Francesco Leri, and Stephen C. Strother
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,Major depressive disorder ,Antidepressant ,medicine.disease ,business ,Biological Psychiatry - Published
- 2019
46. T97. Predicting Functioning and Quality of Life Using Objective and Subjective Measures of Sleep and Biological Rhythms in Major Depressive and Bipolar Disorder
- Author
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Matthew Skelly, Roberto B. Sassi, Maha Eltayebani, Claudio N. Soares, Xiamin Leng, Sidney H. Kennedy, Benicio N. Frey, Luciano Minuzzi, Anastasiya Slyepchenko, and Olivia R Allega
- Subjects
Chronobiology ,Quality of life (healthcare) ,business.industry ,Medicine ,Bipolar disorder ,business ,medicine.disease ,Sleep in non-human animals ,Biological Psychiatry ,Clinical psychology - Published
- 2019
47. The comparative effectiveness of electroencephalographic indices in predicting response to escitalopram therapy in depression: A pilot study
- Author
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Baskaran, Anusha, primary, Farzan, Faranak, additional, Milev, Roumen, additional, Brenner, Colleen A., additional, Alturi, Sravya, additional, Pat McAndrews, Mary, additional, Blier, Pierre, additional, Evans, Ken, additional, Foster, Jane A., additional, Frey, Benicio N., additional, Giacobbe, Peter, additional, Lam, Raymond W., additional, Leri, Francesco, additional, MacQueen, Glenda M., additional, Müller, Daniel J., additional, Parikh, Sagar V., additional, Rotzinger, Susan, additional, Soares, Claudio N., additional, Strother, Steven C., additional, Turecki, Gustavo, additional, and Kennedy, Sidney H., additional
- Published
- 2018
- Full Text
- View/download PDF
48. Premenstrual Dysphoric Disorder: Contemporary Diagnosis and Management
- Author
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Reid, Robert L., primary and Soares, Claudio N., additional
- Published
- 2018
- Full Text
- View/download PDF
49. Performance of the biological rhythms interview for assessment in neuropsychiatry: An item response theory and actigraphy analysis
- Author
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Allega, Olivia R., primary, Leng, Xiamin, additional, Vaccarino, Anthony, additional, Skelly, Matthew, additional, Lanzini, Mariana, additional, Hidalgo, Maria Paz, additional, Soares, Claudio N., additional, Kennedy, Sidney H., additional, and Frey, Benicio N., additional
- Published
- 2018
- Full Text
- View/download PDF
50. Integrated Genome-Wide Methylation and Expression Analyses Reveal Functional Predictors of Response to Antidepressants
- Author
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Ju, Chelsey, primary, Fiori, Laura M., additional, Belzeaux, Raoul, additional, Theroux, Jean-Francois, additional, Chen, Gary Gang, additional, Aouabed, Zahia, additional, Blier, Pierre, additional, Farzan, Faranak, additional, Frey, Benicio N., additional, Giacobbe, Peter, additional, Lam, Raymond W., additional, Leri, Francesco, additional, MacQueen, Glenda M., additional, Milev, Roumen, additional, Müller, Daniel J., additional, Parikh, Sagar V., additional, Rotzinger, Susan, additional, Soares, Claudio N., additional, Uher, Rudolf, additional, Li, Qingqin, additional, Foster, Jane A., additional, Kennedy, Sidney H., additional, and Turecki, Gustavo, additional
- Published
- 2018
- Full Text
- View/download PDF
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